1. Field of the Invention
This invention relates to a process for producing porous, spherical particles of cellulose fatty acid esters. The spherical particles produced by the process of this invention are excellent in particle size uniformity, sphericity and porosity, and can be saponified into spherical particles of cellulose. Both of them are useful as column packing materials for chromatography and additives or excipients for various other purposes.
2. Description of the Prior Art
Fine particles of polymers have been used as additives for plastics, excipients for medical preparations and antiblocking agents, and in many other fields such as cosmetic and printing industries. Recently, these are receiving attention also as carriers to immobilize enzymes and microorganisms, and as packing materials for chromatography. Of various types of polymers, cellulose fatty acid esters, which are particularly soluble in organic solvents and can be easily converted into fine particles, have been extensively used for the purposes mentioned above. In addition, it is also possible to convert the fine particles of cellulose fatty acid esters into particles of cellulose by hydrolysis, or to introduce other functional groups (for example, ion-exchangeable groups) into the molecules of cellulose fatty acid ester, for specific application.
Methods have previously been proposed for the manufacture of spherical particles. For example, a cellulose fatty acid ester may be dissolved in a low-boiling chlorinated hydrocarbon (e.g., dichloromethane), or a solvent mixture containing the same as the main component, the solution thus obtained subjected to dry spinning, and the filaments formed cut into chips, which are then melted by heating in a high-boiling medium (e.g., silicone oil), thus giving spherical particles of the cellulose fatty acid ester. In another method, the solution prepared above is added to an aqueous medium with stirring to form droplets, the resulting dispersion is heated to evaporate the solvent from the droplets, and the spherical particles of cellulose fatty acid ester thus prepared are then saponified into particles of cellulose. [Japanese Patent Publication No. 39565 and No. 40618 (1980)]
These methods, however, involve many steps and consume much energy. Furthermore, the particles of cellulose fatty acid ester obtained are relatively dense in structure, and hence the resulting particles of cellulose are also dense, with the porosity being too low for use as the packing materials for chromatography and for use in sustained release drugs.
The following methods have also been proposed to obtain spherical particles of high porosity. For example, a cellulose fatty acid ester may be dissolved in a low-boiling chlorinated hydrocarbon, or a solvent mixture containing the same as the main component, together with a water-soluble polymer that differs in solubility in the chlorinated hydrocarbon solvent from the cellulose fatty acid ester. The solution thus prepared is added to an aqueous medium with stirring to form droplets, the resulting dispersion is heated to evaporate the solvent from the droplets, and the spherical particles of cellulose fatty acid ester thus prepared are then saponified and freed from the water-soluble polymer, giving spherical particles of cellulose. [Japanese Patent Kokai No. 55055 (1979)] In another method, a high-boiling solvent, such as a higher aliphatic alcohol of 6 to 18 carbon atoms (for example, n-octanol), is added when dissolving the cellulose fatty acid ester in the low-boiling chlorinated hydrocarbon or a solvent mixture containing the same as the main component. The solution thus prepared is added to an aqueous medium with stirring to form droplets, and the resulting dispersion is heated to evaporate the low-boiling solvent from the droplets. The spherical particles of cellulose fatty acid ester containing the high-boiling solvent thus prepared are then saponified and freed from the high-boiling solvent, giving spherical particles of cellulose. [Japanese Patent Kokai No. 24429 (1981)]
In the latter method, in which the low-boiling solvent is removed from droplets by heating, the size of the pores in the porous particles, as well as the diameter, density and other properties of the particles, tend to vary because of the thermoplasticity of cellulose fatty acid esters, thus requiring complex process control to obtain final products of consistent quality. In the former method, in which the water-soluble polymer is removed from the droplets by washing, a high porosity can be achieved but the sizes of individual pores are rather large and their number is limited. Such porous particles containing rather large pores may be used as the carrier to immobilize enzymes and microorganisms and as the starting material for the manufacture of ion-exchangeable cellulose derivatives, but are not suitable as, the packing materials for chromatographic separations of proteins and enzymes.